Reuten, Raphael ORCID: 0000-0002-9434-4108, Patel, Trushar R. ORCID: 0000-0003-0627-2923, McDougall, Matthew, Rama, Nicolas ORCID: 0000-0003-1614-7755, Nikodemus, Denise ORCID: 0000-0003-4492-817X, Gibert, Benjamin, Delcros, Jean-Guy, Prein, Carina, Meier, Markus ORCID: 0000-0003-1068-746X, Metzger, Stephanie, Zhou, Zhigang, Kaltenberg, Jennifer, Mckee, Karen K., Bald, Tobias ORCID: 0000-0003-0061-235X, Tueting, Thomas, Zigrino, Paola ORCID: 0000-0002-7470-0064, Djonov, Valentin ORCID: 0000-0002-5062-1169, Bloch, Wilhelm, Clausen-Schaumann, Hauke ORCID: 0000-0002-9413-0310, Poschl, Ernst, Yurchenco, Peter D., Ehrbar, Martin ORCID: 0000-0003-2707-4870, Mehlen, Patrick, Stetefeld, Jorg and Koch, Manuel (2016). Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Nat. Commun., 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin gamma 1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Reuten, RaphaelUNSPECIFIEDorcid.org/0000-0002-9434-4108UNSPECIFIED
Patel, Trushar R.UNSPECIFIEDorcid.org/0000-0003-0627-2923UNSPECIFIED
McDougall, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rama, NicolasUNSPECIFIEDorcid.org/0000-0003-1614-7755UNSPECIFIED
Nikodemus, DeniseUNSPECIFIEDorcid.org/0000-0003-4492-817XUNSPECIFIED
Gibert, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delcros, Jean-GuyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prein, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, MarkusUNSPECIFIEDorcid.org/0000-0003-1068-746XUNSPECIFIED
Metzger, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, ZhigangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaltenberg, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mckee, Karen K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bald, TobiasUNSPECIFIEDorcid.org/0000-0003-0061-235XUNSPECIFIED
Tueting, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zigrino, PaolaUNSPECIFIEDorcid.org/0000-0002-7470-0064UNSPECIFIED
Djonov, ValentinUNSPECIFIEDorcid.org/0000-0002-5062-1169UNSPECIFIED
Bloch, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clausen-Schaumann, HaukeUNSPECIFIEDorcid.org/0000-0002-9413-0310UNSPECIFIED
Poschl, ErnstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yurchenco, Peter D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehrbar, MartinUNSPECIFIEDorcid.org/0000-0003-2707-4870UNSPECIFIED
Mehlen, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stetefeld, JorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-255311
DOI: 10.1038/ncomms13515
Journal or Publication Title: Nat. Commun.
Volume: 7
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-CONE ATTRACTION; CRYSTAL-STRUCTURE; AXON OUTGROWTH; LAMININ; BINDING; CHAIN; CELL; IDENTIFICATION; EXPRESSION; RECEPTORSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25531

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